Biocompatible prosthesis

ABSTRACT

A method of producing a biocompatible prosthesis based on a substrate made essentially of metal or ceramic. The substrate is placed into a reactor chamber of a cathodic vapor deposition arrangement and the chamber is evacuated to a predetermined pressure. A predetermined, negative bias voltage is then applied to the substrate and the substrate is surface treated by adding an etching gas to the reactor chamber, at a predetermined, first flow rate and coupling in a high frequency power with a first, predetermined power density for ionic etching for a first, predetermined period of time. The surface treated substrate is separated from the negative bias voltage and a semiconductor cover layer is chemical vapor-phase deposited on the substrate by adding to the reactor chamber a multi-component mixture of process gases containing a semiconductor element in bound format a second, predetermined flow rate and coupling-in of HF power with a predetermined, second power density, for a second, predetermined time period.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the right of priority with respect Germanapplication P 44 29 380.1 filed in Germany on Aug. 15, 1994, thedisclosure of which is incorporated herein by reference.

BACKGROUND OF THE INVENTION

The invention relates to a method of producing a biocompatibleprosthesis and, in particular, a non-collapsing, intravascularprosthesis, such as a stent, made essentially of either metal or ceramicand to a prosthesis made by the method.

Cardiovascular implants can be used in the human body particularly asheart valve prostheses or vascular prostheses or pacemaker electrodes.The surface of the implant must possess high blood compatibility(antithrombogenity).

Generic implants as disclosed in European application EP 0 371 908 B1and having a coating of, for example, silicon carbide (SIC),particularly with an amorphous layer structure, have for the most partachieved satisfactory parameters with regard to blood compatibility.These coatings, which possess high quality, can be produced in a simplemanner by a plasma-enhanced vapor-phase deposition (PECVD) method, asdisclosed in detail in U.S. Pat. No. 5,238,866.

The formation of the coating on the substrate is effected at relativelyhigh temperatures of around 250° C., possibly up to 350° C., so thatstructural tensions which limit the adherence of the coating ariseduring cooling.

In connection with percutaneous transluminal coronary angioplasty(PTCCA), which has been practiced in the last few years and has beenintensively advanced systematically, the use of intravascularlyexpandable, non-collapsing vascular prostheses or stents, has achievedsignificance.

In an implant that is subjected to considerable material deformationduring use, it is necessary that the implant have good plastic ductilitywith a suitable yield point to permit sufficient, uniformelongation totake place. This requires an extraordinarily strong adherence betweenthe substrate and the biocompatible coating. The adherence must preventa detachment of the coating, even when relatively severe deformations ofthe substrate occur.

SUMMARY OF THE INVENTION

It is an object of the invention to provide a method of producing avascular prosthesis of the generic type mentioned at the outset whichhas a surface layer that is compatible with blood and has very goodadherence to the substrate material, particularly high-grade steel.

The above and other objects are accomplished in accordance with theinvention by the provision of a method of producing a biocompatibleprosthesis based on a prefabricated substrate comprised essentially ofeither metal or ceramic, the method comprising: placing the substrateinto a reactor chamber of a cathodic vapor deposition arrangement andevacuating the chamber to a predetermined pressure; surface treating thesubstrate by applying a predetermined, negative bias voltage to thesubstrate, and adding an etching gas, at a predetermined, first flowrate and coupling in a high frequency (HF) power, with a first,predetermined power density, into the reactor chamber for ionic etchinga surface of the substrate for a first, predetermined period of time;separating the surface-treated substrate from the negative bias voltage;and chemical vapor-phase depositing a semiconductor cover layer on thesurface of the substrate by adding a multi-component mixture of processgases containing a semiconductor element in bound form at a second,predetermined flow rate and coupling-in of HF power, with apredetermined, second power density, into the reactor chamber for asecond, predetermined time period.

As a result of the method of the invention, the substrate surface isthoroughly cleansed of adsorbates, particularly hydrocarbons and oxides,prior to the application of the biocompatible coating. Further anaugmentation of defects in the substrate surface is effected in order tocreate favorable preconditions for a stable chemical and physicalbonding of the applied coating at a boundary layer. Finally, theinvention utilizes an arrangement that is necessary anyway for layerformation.

According to a another aspect of the invention, a further increase inadhesion can be attained in an advantageous manner in that anintermediate step is performed after the surface treatment of theprefabricated prosthesis. This step involves applying a predetermined,second, negative bias voltage to the surface-treated substrate,supplying a process gas containing the semiconductor material in boundform at a predetermined flow rate, and coupling HF power having apredetermined power density into the sputter reactor for a given timeperiod in order to perform a plasma-enhanced deposition of a thinbonding agent layer that contains the semiconductor element.

The semiconductor element is preferably silicon, and the semiconductorcover layer contains silicon carbide, or is essentially composed ofsilicon carbide. In particular, the cover layer is embodied as anamorphous layer. Its thickness is preferably a few hundred nm,particularly approximately 400 nm.

An inert gas, particularly argon, nitrogen or carbon tetrachloride, ispreferably used as the etching gas in the step of surface treatment,whereas in the step of vapor-phase deposition, the mixture of processgases preferably includes monosilane.

When a silicon-bonding layer is used, the bonding agent layeressentially comprises silicon. The process gas used in forming thebonding agent layer can also preferably be monosilane, and the thicknessof the bonding agent layer is preferably a few nm, and more preferablyabout 3 to 5 nm.

A prefabricated prosthesis, or stent, preferably of high-grade steel,but alternatively of a titanium or tantalum alloy or platinum/iridium,is used as the substrate.

An important factor for good adhesion of the coating on the substrate isthat the temperature of the prefabricated prosthesis be kept constant,preferably at about 250° C., during the entire process. This preventsthe formation of layer tensions during the process. For this purpose,during the transition to the chemical vapor-phase deposition andexecution of this step, the prosthesis is heated by essentiallyinertia-free substrate heating, because in this phase essentially nomore heating takes place through ion bombardment.

To prevent a deposit of residual gases on the surface of the prosthesisbetween process steps, the separation of the substrate from the negativebias voltage advantageously takes place without interrupting thecoupling-in of the HF power, i.e. the plasma is maintained in thereactor chamber.

Due to a continuous change of the process gas composition over a givenperiod of time, the bonding agent layer and the semiconductor coverlayer can be formed so as to blend at an increasing distance from thesurface of the prefabricated substrate, and not possess a distinctiveboundary surface, with the component of the semiconductor element, forexample elementary Si, being removed.

In another aspect of the invention, there is provided a biocompatibleprosthesis comprising a prefabricated substrate made essentially ofmetal or ceramic and having a semiconductor cover layer covering itssurface, wherein there is a boundary surface formed between the surfaceof the substrate and the semiconductor cover layer whose microstructureis characterized by reciprocal bumps and dents and an alloy-likechemical structure.

Both the substrate material that is near the surface and the boundarysurface are essentially free from oxygen and/or hydrocarbons, which ispartially responsible for the good adhesiveness of the cover layer.

In a preferred embodiment, the boundary layer is formed between themetal or ceramic surface of the prefabricated substrate and the bondingagent layer of semiconductor material.

Other advantages, features and modifications of the invention will beappreciated from the following detailed description of the inventionwhen considered in conjunction with the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic, cross-sectional representation of the layerstructure in an embodiment of the prosthesis produced according to theinvention.

FIG. 1a is an enlarged, representation of the circled area in FIG. 1.

FIG. 2 is a schematic cross-section showing a first stage of the methodof the invention in which the prefabricated substrate is given anultrasound bath.

FIGS. 2a through 2c are schematic representations including blockcircuit diagrams used to explain further steps of the method of theinvention.

FIGS. 3a and 3b are schematic representations of the potential curvebetween the electrodes of the device in different steps, respectively.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Referring to FIG. 1, there is shown a schematic, cross-sectionalrepresentation of the layer structure of an antithrombogenic prosthesis,in this case a stent 1, made according to the invention, for use in thetherapy of coronary vascular stenoses. FIG. 1 is not to scale withrespect to the layer thickness ratios.

Stent 1 comprises a substrate 2, for example of 316L high-grade steel,on which there is formed an intermediate layer 3 of amorphous silicona--Si having a thickness of about 3-5 nm and, on this layer, there isformed a cover layer 4 of amorphous, n-doped silicon carbide a--SiC:Hhaving a thickness of about 400 nm. Intermediate layer 3 and cover layer4 are not separated from each other by a defined boundary surface, butrather blend into one another.

FIG. 1a shows an enlargement of the circled area A in FIG. 1. It can beseen here that the boundary surface between substrate 2 and intermediateor bonding agent layer 3 is not even, but has a severely fissuredmicrostructure, i.e. there is a boundary surface 2/3 (shown betweendashed lines in FIG. 1a) having interlocked bumps and dents of adjacentmaterials that are fused in an alloy-like structure. Boundary surface3/4 between bonding agent layer 3 and cover layer 4 has a similarmicrostructure, in which the carbon component increases from the bottomto the top.

It is significant for the function of bonding agent layer 3 that therebe practically no foreign atoms, particularly oxide or hydrocarbondeposits, on the substrate material in the region of the bonding agentlayer, including its boundary surfaces.

FIGS. 2a through 2c are schematic representations for clarification ofthe essential steps of the method for applying the biocompatible,adhesive coating to a prosthesis, such as a stent, according to anembodiment of the invention.

FIG. 2 illustrates a first method stage (a), in which a prefabricatedsubstrate S of 316L high-grade steel and having the shape of theprosthesis, or stent, is first cleaned in an isopropanol bath 10 bymeans of ultrasound supplied by a conventional ultrasound transmitter11.

Referring to FIG. 2a, in a second stage (b), substrate S is subjected toa plasma enhanced ionic etching or a reactive ionic etching treatment ina reactor chamber 21 of a parallel-plate reactor arrangement 20. Inaddition to the actual reactor chamber 21, reactor arrangement 20includes a d.c. voltage source 22 that has a cut-off switch 22a; an HFtransmitter 23 that has a matching network 23a; a gas supply 24 that hasa flow-regulating and measuring unit 24a; a vacuum-generating system 25;a pressure-measuring unit 26 that has an absolute pressure sensor 26a; atemperature measurement and control unit 27 that has a pyroelectricT-detector 27a; and a process-control unit 28.

In a practical embodiment of arrangement 20, temperature measurement andcontrol unit 27 includes a group of halogen lamps (not shown in thedrawings) aimed at substrate S to effect a nearly inertia-freeadditional heating of the substrate.

In stage (b), reactor chamber 21 is initially evacuated to a pressure ofless than 10⁻⁸ bar, and substrate S is preheated to 250° C. forapproximately 10 minutes.

Following this step, only the valve of the Ar (argon) container isopened in gas supply 24, whereas the valves of the other gas containersare closed. Argon is admitted into reactor chamber 21 through gas supply24. With a gas flow of up to approximately 40 sccm, a pressure in arange of 2×10⁻⁶ to 10⁻⁵ bar is established.

In FIGS. 2a and 2b, cut-off switch 22a of d.c. voltage supply 22 isclosed thereby applying a negative bias voltage (in a range ofapproximately 500 to approximately 1500 volts, preferably 1000 volts) tosubstrate S. Substrate S is thus cathodically polarized in this methodstage, in which the bias voltage is established according to theparameters of the arrangement and the desired end product. In addition,HF transmitter 23 couples into reactor chamber 21 HF power with powerdensity in a range of 0.16 W/cm² for a period of 10 to 15 minutes.During this period the temperature of substrate S is kept substantiallyconstant at about 250° C.

In this phase, ionic etching of the surface of substrate S takes placeunder the conditions disclosed above. In the process, deposits,particularly of hydrocarbons, are effectively removed, and an increasein the defect density on the surface occurs. This creates advantageouspreconditions for the formation of stable chemical bonds betweensubstrate S and a layer applied directly thereafter.

The next method stage (c) is likewise performed in reactor arrangement20, as shown schematically in FIG. 2b. In this stage, the valve of theargon container is closed, and the valve of the SiH₄ container is open.The gas flow is at 40 sccm, and the process gas pressure is at 4×10⁻⁵bar. Substrate S is further acted upon by a negative bias voltage thatmay be in the same range as in stage (b) or preferably even above it (atapproximately 2000 V). The temperature is again kept substan-tiallyconstant at about 250° C.

In this stage the surface of substrate S is subjected to a high-energybombardment with silicon. This bombardment leads to a furtherstructuring of the surface and, simultaneously, to the deposit ofamorphous silicon (a--Si). After a process length of a few(approximately five) minutes, this forms a 3 to 5 nm thick layer that isclosely interlocked with the substrate surface. Interdiffusion processesalong the crystal boundaries in this layer lead to the formation ofchemical bonds between components of the substrate and the silicon.

A fourth and essential stage (d) of the method is likewise performed inreactor arrangement 20, as can be seen in FIG. 2c. In this stage, thevalves of the monosilane (SiH₄) and methane (CH₄) containers in gassupply 24 are both open. The individual flow rates for (SiH₄) and (CH₄),which in practice are additionally mixed with a small amount ofphosphine, are controlled individually by process control unit 28 tocorrespond to the desired elementary proportions of Si and C in thelayer to be deposited. Advantageous settings of the gas flows have beenfound to be 35.5 sccm for SiH₄, 3.53 sccm for CH₄ and 37.2 sccm for PH₃.The process gas pressure is 8×10⁻⁵ bar, and the substrate temperature isagain 250° C. The substrate temperature can only be reached with theadditional halogen heating in this method stage, because no more warmingdue to ion bombardment takes place.

In stage (d), cut-off switch 22a is open so that a d.c. voltage is nolonger applied to the electrodes and the electrode that receives thesubstrate is grounded. Thus, in this stage (d), the substrate is notacted upon by a d.c. bias voltage. Rather, stage (d) of the method isperformed with capacitively coupled-in HF power supplied by HF stage 23at, for example 13.56 MHz with a power density of 0.16 W/cm².

Over the course of this latter stage of the method, known asplasma-enhanced, chemical vapor-deposition (PECVD), a layer having athickness of a few hundred, preferably 400 nm, and made of amorphoussilicon carbide (a--SiC) is deposited on the high-grade-steel substrateS (more precisely, on the thin a-Si layer covering the substrate) in anSiH₄ /CH₄ atmosphere with a gas composition that has been predeterminedby the valves of gas supply 24. Since the supply of the monosilane doesnot take place abruptly when the corresponding valve is opened, thelayer of pure Si and the SiC layer blend as the C component is graduallyadded. This completes the biocompatible stent.

The biocompatible SiC layer has outstanding adhesiveness that isexpressed in a significantly increased critical strength in aconventional scratch test.

FIGS. 3a and 3b are schematic representations of the potential curvebetween the electrodes of the device in step (b) according to FIGS. 2aand step (d) according to FIG. 2c. An upper electrode E supports thesubstrate. The HF power from HF stage 23 is capacitively coupled into alower electrode E2. In stages (b) and (c), a high negative bias voltageis applied to upper electrode E1 as shown in FIG. 3a. In stage (d), E1is grounded as shown in FIG. 3b.

The process gas particles are very effectively ionized by the potentialcurve illustrated in FIG. 3a, and high ionic currents that lead to aneffective removal of impurities are accelerated onto the surface ofsubstrate S. In the transition to the coating of cover layer 4,according to FIG. 3b, only the d.c. voltage is cut off, in which casethe plasma is retained and no interruptions of the process occur thatwould disadvantageously lead to a deposit of residual gases on thesurface, and thus to a deterioration of the adhesiveness.

The implementation of the illustrated potential curves requires the useof filters that prevent, on the one hand, a coupling of the HF into thed.c. voltage source and, on the other hand, a mutual influence betweend.c. voltage source 22 and HF generator 23. These are included inmatching network 23a.

The illustrated shape and position of the components of reactorarrangement 20, as well as the position of substrate S in thisarrangement, are to be understood solely in the sense of a purelyschematic representation. The arrangement can be modified in numerousways. In a different structure, altered power densities and gas flowsthat may also be essential for the creation of an optimum layer must beestablished.

The above-described method can also be employed, with appropriatelyvaried materials and method parameters, with other implantationmaterials, and with other biocompatible layers. In particular, a similarcoating of titanium alloys (e.g. TiAl5Fe2,5), tantalum,platinum/iridium, pyrolytic carbon or oxide ceramic (e.g. ZrO₂) witha--SiC is possible. In principle, other semiconductive coating materialshaving suitable band gaps can be used, in which case the selection ofthe process gases is, of course, a function of the chemical compositionof the layer to be produced, but is also to be regarded as beingbasically known for a certain layer composition. However, according tothe investigations conducted by the inventors, SiC is to be regarded asan advantageous material in numerous aspects.

The step of applying the intermediate layer can also be omitted. Theembodiment of method stages (b) and (d) according to FIGS. 2a and 2c isto be considered essential to the invention.

The invention is not limited in its embodiment to the above-disclosed,preferred embodiment. Rather, a number of variations are conceivablewhich utilize the illustrated solution, even in fundamentally differenttypes of configurations.

The invention has been described in detail with respect to preferredembodiments, and it will now be apparent from the foregoing to thoseskilled in the art that changes and modifications may be made withoutdeparting from the invention in its broader aspects, and the invention,therefore, as defined in the appended claims is intended to cover allsuch changes and modifications as fall within the true spirit of theinvention.

What is claimed is:
 1. A biocompatible prosthesis, comprising:aprefabricated substrate comprised of one of a metallic and a ceramicmaterial; a cover layer including a semiconductor material covering asurface of the substrate; and a boundary layer having a microstructureincluding reciprocal bumps and dents formed between the surface of thesubstrate and the cover layer said bumps and dents interlocking saidsubstrate and said cover layer.
 2. The biocompatible prosthesisaccording to claim 1, further comprising a semiconductor bending agentlayer comprised of the same semiconductor material as the cover layerand being disposed between the boundary layer and the cover layer. 3.The biocompatible prosthesis according to claim 1, wherein the boundarylayer has an alloy-type chemical structure.
 4. The biocompatibleprosthesis according to claim 1, wherein the surface of the substrateand the boundary layer are essentially free from oxygen andhydrocarbons.